There are three major studies contributed during FY2010 under this project heading. Together with the Domachowske laboratory (Pediatric Infectious Diseases / Virology / SUNY Upstate Medical University) we have performed a retrospective clinical analysis of inflammatory mediators detected in nasal wash samples from pediatric patients with documented parainfluenza (PIV) infection. Specifically, archived nasal wash samples (1998 - 2008) were assayed for 26 unique inflammatory mediators using Luminex bead proteomics analysis. Compared with uninfected control patients, elevated concentrations of IL-6, IL-8, CCL3, CCL4, CXCL9, and CCL5 were detected in nasal wash samples from PIV-infected patients. Among other findings, we concluded that PIV infection results in a spectrum of illnesses, with elevated concentrations of IL-8 in nasal wash samples associated with more severe forms of disease (El Feghaly et al. Pediatr Infect Dis J 2010). This is the first of a series of three collaborative clinical studies focusing on inflammatory responses to paramyxovirus infection;two additional studies will follow in FY2011. I also contributed to a study carried out by my collaborator and former student, Dr. Reinout Bem (Academic Med Ctr, Amsterdam), which utilized the pneumonia virus of mice (PVM) natural rodent pathogen model developed in my lab to explore the role of granzymes in promoting inflammatory lung injury. Although neither granzyme A nor granzyme B deficiency had any impact on virus recovery, deficiency of these cytotoxic T lymphocyte proteins results in delayed clinical response to fatal pneumovirus infection, a feature that is likewise associated with delayed neutrophil recruitment, diminished activation of caspase-3, and reduced lung permeability. We conclude that granzyme A- and B-cluster deficiency delays the acute progression of pneumovirus disease by reducing alveolar injury (Bem et al. J. Immunol. 2010). Likewise, I contributed to a study performed in collaboration with Dr. Rakesh Kumar (UNSW) and Dr. Paul Foster (University of Newcastle) which featured the natural rodent pathogen PVM model to examine the combined impact of virus infection and antigen challenge toward the development of allergic lung inflammation in neonatal mice (see also AI000941-07). Among our conclusions,we noted that interaction between viral infection and allergen sensitization/challenge is essential for development of the characteristic features of childhood asthma in the neonatal mouse model, including allergic inflammation and a Th2-biased immune response.